Oral lyophilisates are solid preparations intended to be placed in the mouth or to be dispersed in water before administration. They are characterized by fast disintegration and thus by rapid dissolution of active substances, which improves their absorption and bioavailability. In our thesis, our goal was to plan a development approach of oral lyophilisates containing olanzapine. We used a quality by design approach and established a knowledge space by market review and scientific literature study. Currently there are 22 oral lyophilisates on the market, most of them with the effect on the nervous system. The most commonly used excipients are mannitol, gelatin, citric acid, NaOH, xanthan gum, glycine and dextran 70. For optimization purposes most commonly surfactants and water-soluble polymers are being used. We determined the quality target product profile and selected critical quality attributes. These are: appearance, mechanical resistance, dissolution, disintegration time and residual moisture. Flow and Ishikawa charts were used for quality risk identification purposes, followed by risk analysis and assessment. Failure mode and effects analysis proved to be insufficient. Additionally, we used color matrices and a color scale to determine risk descriptors. The critical material attributes were selection, % and intrinsic moisture content of excipients, particle size, crystallinity/ amorphousness and solubility of the active substance. The selected critical process parameters were cooling rate; shelf temperature, drying chamber pressure and primary drying time; shelf temperature and secondary drying time. We used Minitab® software and data from the Department of Pharmaceutical Technology to establish a design space. We employed linear regression and factorial design (2x4) to set up a model with good predictive power and proposed an optimized formulation. We concluded that the formulation optimally contains 6 % of excipients, among which mannitol predominates, higher % PVP K25 are not desirable and it must contain a higher % of mannitol than PVP K25. Our results are approaching their optimal ratio which must be at least 1:5. Gelatin is essential for the incorporation of olanzapine, which we could not recognize with the use of the software. The model represents an approximation of values that can help in the pharmaceutical development and can also prevent unnecessary effort, time and resources investment.
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